Oim mice exhibit altered femur and incisor mineral composition and decreased bone mineral density

To investigate the role of the pro alpha 2(I) collagen chains of type I col lagen in mineralization we used the oim (osteogenesis imperfecta model) mou se as our model system. The oim/oim mouse (homozygous for a null mutation i n its COL1A2 gene of type I collagen) fails to synthesize functional pro al pha 2(I) collagen chains, synthesizing only homotrimers of pro alpha 1(I) c ollagen chains. To evaluate the role of pro alpha 2(I) collagen in type I c ollagen structure/function in mineralized tissues, we examined age-matched oim/oim, heterozygous (oim/+), and wild-type (+/+) mouse femurs and incisor s for mineral composition (calcium, phosphorus, magnesium, fluoride, sodium , potassium, and chloride) by neutron activation analyses (NAA), and bone m ineral content (BMC) and hone mineral density (BMD) by dual-energy X-ray ab sorptiometry (DEXA) in a longitudinal study (7 weeks to 16 months of age). NAA demonstrated that oim/oim femurs had significant differences in magnesi um, fluoride, and sodium content as compared with +/+ mouse femurs, and oim /oim teeth had significant differences in magnesium content as compared to +/+ teeth. The ratio of calcium to phosphate was also significantly reduced in the oim/oim mouse femurs (1.58 +/- 0.01) compared with +/+ femurs (1.63 +/- 0.01). DEXA demonstrated that oim/oim mice had significantly reduced B MC and BMD as compared to oim/+ and +/+ mice. Serum and urine calcium, magn esium, and phosphorus levels, and Ca-47 absorption across the gut were equi valent in oim/oim and +/+ mice, with no evidence of hypercalciuria. These s tudies suggest that the known decreased biomechanical properties of oim/oim bone reflect both altered mineral composition as well as the decreased BMD , which further suggests that the presence of alpha 2(I) chains plays an im portant role in mineralization. (C) 2000 by Elsevier Science Inc. All right s reserved.